Human Immunodeficiency Virus Antiretroviral Resistance and Transmission in Mother-Infant Pairs Enrolled in a Large Perinatal Study

Abstract

Background: The presence of antiretroviral drug-associated resistance mutations (DRMs) may be particularly problematic in human immunodeficiency virus (HIV)-infected pregnant women as it can lead to mother-to-child transmission (MTCT) of resistant HIV strains. This study evaluated the prevalence and the effect of antiretroviral DRMs in previously untreated mother-infant pairs.

Methods: A case-control design of 1:4 (1 transmitter to 4 nontransmitters) was utilized to evaluate DRMs as a predictor of HIV MTCT in specimens obtained from mother-infant pairs. ViroSeq HIV-1 genotyping was performed on mother-infant specimens to assess for clinically relevant DRMs.

Results: One hundred forty infants acquired HIV infection; of these, 123 mother-infant pairs (88%) had specimens successfully amplified using ViroSeq and assessed for drug resistance genotyping. Additionally, 483 of 560 (86%) women who did not transmit HIV to infants also had samples evaluated for DRMs. Sixty-three of 606 (10%) women had clinically relevant DRMs; 12 (2%) had DRMs against >1 drug class. Among 123 HIV-infected infants, 13 (11%) had clinically relevant DRMs, with 3 (2%) harboring DRMs against >1 drug class. In univariate and multivariate analyses, DRMs in mothers were not associated with increased HIV MTCT (adjusted odds ratio, 0.8 [95% confidence interval, .4-1.5]). Presence of DRMs in transmitting mothers was strongly associated with DRM presence in their infants (P < .001).

Conclusions: Preexisting DRMs were common in untreated HIV-infected pregnant women, but did not increase the risk of HIV MTCT. However, if women with DRMs are not virologically suppressed, they may transmit resistant mutations, thus complicating infant management.

Figure 1.

Flowchart of human immunodeficiency virus–infected mothers (A) and infants (B) included in this study. *Twelve mothers and 3 infants with drug-associated resistance mutations against >1 class of antiviral. Abbreviations: DRM, drug-associated resistance mutation; HIV, human immunodeficiency virus; NNRTI, nonnucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Figure 2.

Graphs showing percentage of mutations found in samples collected from human immunodeficiency virus (HIV)–infected mothers (blue, n = 606) and in infants (red, n = 123). Asterisk (*) marks mutations included in our analysis as clinically relevant mutations, and plus signs (+) refer to mutations that in conjunction with another mutation were clinically relevant. These were assigned by study investigators based on the Stanford University HIV Drug Resistance Database (http://hivdb.stanford.edu/DR) at the time the study was conducted. Abbreviations: NNRTI, nonnucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.